Review
Geriatrics & Gerontology
Jiang Chen, Jun-Sheng Chen, Song Li, Fengning Zhang, Jie Deng, Ling-Hui Zeng, Jun Tan
Summary: Decades of research have shown that amyloid-beta (Aβ) plays an undeniable role in the development of Alzheimer's disease (AD). However, the focus on the pathological effects of Aβ may overshadow the significance of its metabolic precursor, amyloid precursor protein (APP), in the occurrence and progression of AD. This review explores the various roles of APP in AD, including its structure, functions, enzymatic processing, and potential therapeutic approaches to targeting APP to ameliorate AD pathologies and halt disease progression.
Review
Biochemistry & Molecular Biology
Kseniia S. Orobets, Andrey L. Karamyshev
Summary: Alzheimer's disease is a common neurodegenerative disorder associated with age or inherited mutations. It is characterized by severe dementia that affects memory, cognitive functions, and daily life. The disease is linked to the accumulation of cytotoxic amyloid beta and hyperphosphorylated tau protein, as well as other pathological features. Various treatment options, such as antibody-based therapy and stem cell transplantation, are being investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Physiology
Jerome Garcia, Rudy Chang, Ross A. Steinberg, Aldo Arce, Joshua Yang, Peter van der Eb, Tamara Abdullah, Devaraj V. Chandrashekar, Sydney M. Eck, Pablo Meza, Zhang-Xu Liu, Enrique Cadenas, David H. Cribbs, Neil Kaplowitz, Rachita K. Sumbria, Derick Han
Summary: Heavy alcohol consumption is a known risk factor for dementia and Alzheimer's disease. However, intragastric alcohol feeding-induced liver steatosis, rather than alcohol-induced liver injury, may be more responsible for disrupting A beta processing by the liver and promoting AD.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Geriatrics & Gerontology
Jinsu Park, Meenu Madan, Srinivasulu Chigurupati, Seung Hyun Baek, Yoonsuk Cho, Mohamed R. Mughal, Amin Yu, Sic L. Chan, Jogi Pattisapu, Mark P. Mattson, Dong-Gyu Jo
Summary: AQP1 levels are elevated in the cerebral cortex during the early stages of AD, particularly in vulnerable neurons, and increase as aging progresses in AD mouse models. AQP1 appears to reduce A beta production by inhibiting the binding between BACE1 and APP.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Xiaoling Liu, Yan Liu, Shangrong Ji
Summary: Alzheimer's disease is a common neurodegenerative disease that increases in prevalence with age. Studies suggest that abnormalities in the metabolism of APP are a major pathological feature of AD, with secretases playing a key role in APP processing. Research on secretases in the processing of APP could potentially lead to new directions for AD therapy.
Review
Neurosciences
Rebecca M. C. Gabriele, Emily Abel, Nick C. Fox, Selina Wray, Charles Arber
Summary: Amyloid precursor protein (APP) and its cleavage fragment Amyloid-beta (A beta) play crucial roles in Alzheimer's disease (AD). Genetic alterations that increase the overall dosage of APP or favor the generation of more aggregation-prone A beta species directly contribute to the disease. Lowering APP expression is an attractive approach for AD treatment and prevention. New technologies that reduce APP expression may offer disease modification and slow clinical progression.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Tong Lin, Lars O. Tjernberg, Sophia Schedin-Weiss
Summary: Alzheimer's disease is a common neurodegenerative disease that primarily affects memory and cognitive abilities, with no known cure. Early diagnosis and understanding of its pathology are crucial for effective management of the disease.
Review
Pharmacology & Pharmacy
Yoonsuk Cho, Han-Gyu Bae, Eitan Okun, Thiruma V. Arumugam, Dong-Gyu Jo
Summary: APP is an evolutionarily conserved transmembrane protein that serves as a precursor to amyloid-beta peptides, which are implicated in Alzheimer's disease. Studies have shown diverse pathological and physiological functions of APP and its cleavage products, but their roles are not fully understood. Current research focuses on APP processing and potential therapeutic approaches for Alzheimer's disease.
PHARMACOLOGY & THERAPEUTICS
(2022)
Review
Cell Biology
Fengjuan Jiao, Dongjun Jiang, Yingshuai Li, Juan Mei, Qinqin Wang, Xuezhi Li
Summary: This review provides a brief summary on the role of neurotrophic dysfunction and the amyloidogenic process in the pathology of Alzheimer's disease (AD). It suggests that these two pathogenesis pathways mutually influence and may commonly contribute to the onset and progression of AD. The involvement of intracellular regulators in both pathogenesis pathways suggests that they may be the shared original causes of amyloidogenesis and neurotrophic dysfunction. Therapeutic strategies targeting the common pathways to prevent amyloidogenesis and neurotrophic dysfunction simultaneously could potentially be used for disease-modifying treatment of AD.
Review
Neurosciences
Lina Gao, Yun Zhang, Keenan Sterling, Weihong Song
Summary: Synaptic abnormalities are a key aspect of Alzheimer's disease, connecting pathological changes to cognitive impairment. Brain-derived neurotrophic factors are crucial in synaptic plasticity for learning and memory, and have potential as diagnostic biomarkers and therapeutic molecules for AD. The exact mechanisms underlying the effects of impaired BDNF signaling on AD are still unclear.
TRANSLATIONAL NEURODEGENERATION
(2022)
Article
Geriatrics & Gerontology
Kenji Yamamoto, Ryo Yamamoto, Nobuo Kato
Summary: In this study, it was found that specific antibodies can recover the activity of BK channels suppressed by Aβ oligomers in neurons of Alzheimer's disease model mice, suggesting an important role of APP in this process.
FRONTIERS IN AGING NEUROSCIENCE
(2021)
Article
Cell Biology
Qi Shen, Xiaolei Wu, Zhan Zhang, Di Zhang, Sihua Yang, Da Xing
Summary: The study found that inducing gamma oscillations with non-invasive light flicker can reduce Alzheimer's disease-related pathology. By increasing the anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing and interacting with KCC2, it helps maintain surface GABA(A) receptor alpha 1 levels and reduce beta-amyloid (A beta) production. These findings highlight the importance of enhancing APP trafficking to the plasma membrane in the reduction of A beta load in Alzheimer's disease.
Article
Neurosciences
Sandra Schilling, Ajay Pradhan, Amelie Heesch, Andrea Helbig, Kaj Blennow, Christian Koch, Lea Bertgen, Edward H. Koo, Gunnar Brinkmalm, Henrik Zetterberg, Stefan Kins, Simone Eggert
Summary: This study compares the effects of different APP genetic mutations on their processing and pathogenic mechanisms in Alzheimer's disease. The results show significant differences in the underlying mechanisms for familial AD mutations located at the alpha-, beta-, and gamma-secretase cleavage sites. Different mutations have different effects on APP processing and the generation of A β peptides.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Neurosciences
Xi-Jun Song, He-Yan Zhou, Yu-Ying Sun, Han-Chang Huang
Summary: Alzheimer's disease is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. The main constituent of senile plaques, Aβ peptide, is derived from AβPP through cleaving by enzymes. Post-translational modifications like phosphorylation and glycosylation of AβPP may affect its trafficking and cleavage.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Review
Endocrinology & Metabolism
Yanjun Guo, Qinqiu Wang, Shenghui Chen, Chengfu Xu
Summary: This article summarizes the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues, indicating that peptides generated by non-amyloidogenic processing can have positive effects on metabolism, while those produced by amyloidogenic processing may have negative impacts. Abnormal expression of APP is associated with metabolic diseases (such as diabetes, obesity, etc.) and cancer.
METABOLISM-CLINICAL AND EXPERIMENTAL
(2021)
Article
Cell Biology
Catherine A. Blizzard, Katherine A. Southam, Edgar Dawkins, Katherine E. Lewis, Anna E. King, Jayden A. Clark, Tracey C. Dickson
DISEASE MODELS & MECHANISMS
(2015)
Article
Neurosciences
Mariana Brizuela, Catherine A. Blizzard, Jyoti A. Chuckowree, Edgar Dawkins, Robert J. Gasperini, Kaylene M. Young, Tracey C. Dickson
MOLECULAR AND CELLULAR NEUROSCIENCE
(2015)
Article
Neurosciences
Emily E. Handley, Kimberley A. Pitman, Edgar Dawkins, Kaylene M. Young, Rosemary M. Clark, Tongcui C. Jiang, Bradley J. Turner, Tracey C. Dickson, Catherine A. Blizzard
Article
Biochemistry & Molecular Biology
Yanling Hu, Amos C. Hung, Hao Cui, Edgar Dawkins, Marta Bolos, Lisa Foa, Kaylene M. Young, David H. Small
JOURNAL OF BIOLOGICAL CHEMISTRY
(2013)
Article
Neurosciences
Edgar Dawkins, Robert Gasperini, Yanling Hu, Hao Cui, Adele J. Vincent, Marta Bolos, Kaylene M. Young, Lisa Foa, David H. Small
JOURNAL OF NEUROSCIENCE RESEARCH
(2014)
Article
Clinical Neurology
David H. Small, Yanling Hu, Marta Bolos, Edgar Dawkins, Lisa Foa, Kaylene M. Young
NEURODEGENERATIVE DISEASES
(2014)
Article
Cell Biology
Tongcui Jiang, Emily Handley, Mariana Brizuela, Edgar Dawkins, Katherine E. A. Lewis, Rosemary M. Clark, Tracey C. Dickson, Catherine A. Blizzard
DISEASE MODELS & MECHANISMS
(2019)
Article
Biochemistry & Molecular Biology
Li Kong, Edgar Dawkins, Frederick Campbell, Edith Winkler, Rico J. E. Derks, Martin Giera, Frits Kamp, Harald Steiner, Alexander Kros
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Edgar Dawkins, Rico J. E. Derks, Martina Schifferer, Johannes Trambauer, Edith Winkler, Mikael Simons, Dominik Paquet, Martin Giera, Frits Kamp, Harald Steiner
Summary: Membrane remodeling can enhance the activity of gamma-secretase, leading to increased production of beneficial A beta species in Alzheimer's disease. However, the effects of membrane remodeling vary in different types of gamma-secretase, highlighting the importance of lipid-based AD treatment strategies.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
C. Blizzard, E. Handley, E. Dawkins, R. Clark, T. Fielder, B. Turner, T. Dickson
JOURNAL OF NEUROCHEMISTRY
(2015)
Article
Biochemistry & Molecular Biology
Pei-Yang Gao, Ya-Nan Ou, Yi-Ming Huang, Zhi-Bo Wang, Yan Fu, Ya-Hui Ma, Qiong-Yao Li, Li-Yun Ma, Rui-Ping Cui, Yin-Chu Mi, Lan Tan, Jin-Tai Yu
Summary: Liver function may play a role in the progression of Alzheimer's disease. The study found that as AD progressed, certain liver function markers increased while others decreased. The relationship between liver function and CSF AD biomarkers indicates a potential mediation effect on cognition.
JOURNAL OF NEUROCHEMISTRY
(2024)